WO1997015550A1 - Derives de l'acide benzoylpropionique substitues par fluoro - Google Patents

Derives de l'acide benzoylpropionique substitues par fluoro Download PDF

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Publication number
WO1997015550A1
WO1997015550A1 PCT/EP1996/004321 EP9604321W WO9715550A1 WO 1997015550 A1 WO1997015550 A1 WO 1997015550A1 EP 9604321 W EP9604321 W EP 9604321W WO 9715550 A1 WO9715550 A1 WO 9715550A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
amino
acid
hydroxy
Prior art date
Application number
PCT/EP1996/004321
Other languages
English (en)
Inventor
Mario Varasi
Antonio Giordani
Carmela Speciale
Massimo Cini
Alberto Bianchetti
Original Assignee
Pharmacia & Upjohn S.P.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmacia & Upjohn S.P.A. filed Critical Pharmacia & Upjohn S.P.A.
Priority to SI9630227T priority Critical patent/SI0862551T1/xx
Priority to AT96934537T priority patent/ATE193522T1/de
Priority to DE69608699T priority patent/DE69608699T2/de
Priority to JP9516233A priority patent/JPH11513694A/ja
Priority to DK96934537T priority patent/DK0862551T3/da
Priority to US09/051,486 priority patent/US5973006A/en
Priority to EP96934537A priority patent/EP0862551B1/fr
Priority to AU72852/96A priority patent/AU7285296A/en
Publication of WO1997015550A1 publication Critical patent/WO1997015550A1/fr
Priority to GR20000401940T priority patent/GR3034253T3/el

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
    • C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/36—Antigestagens
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings

Definitions

  • the scope of the present invention encompasses both the individual optical isomers and the racemic mixture of the formula (I) compounds.
  • R are hydroxy, amino, hydroxylamino or OR' in which R' is C 1 -C 6 alkyl and benzyl .
  • the term C x -C 6 alkyl includes, for example C 1 -C 1 alkyl such as methyl, ethyl, n-propyl, isopropyl and n- butyl; preferably, it is methyl, ethyl or n-propyl.
  • R-, in the above formulae (III) and (IV) is trifluoromethyl, methoxy or ethoxy.
  • the reaction of a compound of formula (II) with a compound of formula (III) , as described under step a) may be carried out according to known methods (see, for example, J.E. Nordlander, J. Org. Chem., 5_0_, 3619-22,
  • the reaction mixture of a total volume of 100 ml was constituted of 44 mg of suspended extract, 100 mM Tris/Cl " buffer pH 8.1, 10 mM EDTA, 100 mM KCl, 0.8 mM NADPH, 0.025 mM L-kynurenine, 0.5 mCi L- (3, 5- 3 H) Kynurenine (10 Ci/mmol) and 10 ml of different concentration of inhibitor solutions. After the incubation the reaction was terminated by the addition of 1 mL of 7.5% (w/v) activated charcoal, vortexed and centrifugated for 7 min. A 500 ml aliquot of supernatant was counted by scintillation spectroscopy in 5 ml of liquid scintillation.
  • the compounds of the present invention were constituted of 44 mg of suspended extract, 100 mM Tris/Cl " buffer pH 8.1, 10 mM EDTA, 100 mM KCl, 0.8 mM NADPH

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

On décrit un dérivé de l'acide benzoylpropionique substitué par fluoro, de la formule (I), ou un sel de celui-ci acceptable sur le plan pharmacologique, soit en tant qu'isomère seul, soit en tant que mélange d'isomères. Dans cette formule, R représente hydroxy, amino, hydroxylamine, -OR', -NHR', N(R')2 ou -NHOR', où R' représente alkyle C1-C6 ou benzyle. Ce dérivé agit en tant qu'inhibiteur de la kynurénine-3-hydroxylase et il peut être utile dans le traitement des maladies neurodégénératives. On décrit encore un procédé de préparation de composés de la formule (I) ainsi que des compositions pharmaceutiques comprenant ceux-ci.
PCT/EP1996/004321 1995-10-20 1996-10-04 Derives de l'acide benzoylpropionique substitues par fluoro WO1997015550A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
SI9630227T SI0862551T1 (en) 1995-10-20 1996-10-04 Fluoro-substituted benzoylpropionic acid derivatives
AT96934537T ATE193522T1 (de) 1995-10-20 1996-10-04 Fluorsubstituierte benzoylpropionsaürederivate
DE69608699T DE69608699T2 (de) 1995-10-20 1996-10-04 Fluorsubstituierte benzoylpropionsaürederivate
JP9516233A JPH11513694A (ja) 1995-10-20 1996-10-04 フルオロ置換ベンゾイルプロピオン酸誘導体
DK96934537T DK0862551T3 (da) 1995-10-20 1996-10-04 Floursubstituerede benzoylpropionsyrederivater
US09/051,486 US5973006A (en) 1995-10-20 1996-10-04 Fluoro-substituted benzoylpropionic acid derivatives
EP96934537A EP0862551B1 (fr) 1995-10-20 1996-10-04 Derives de l'acide benzoylpropionique substitues par fluoro
AU72852/96A AU7285296A (en) 1995-10-20 1996-10-04 Fluoro-substituted benzoylpropionic acid derivatives
GR20000401940T GR3034253T3 (en) 1995-10-20 2000-08-23 Fluoro-substituted benzoylpropionic acid derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9521486.2A GB9521486D0 (en) 1995-10-20 1995-10-20 Fluoro-substituted benzoylpropionic acid derivatives
GB9521486.2 1995-10-20

Publications (1)

Publication Number Publication Date
WO1997015550A1 true WO1997015550A1 (fr) 1997-05-01

Family

ID=10782602

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1996/004321 WO1997015550A1 (fr) 1995-10-20 1996-10-04 Derives de l'acide benzoylpropionique substitues par fluoro

Country Status (14)

Country Link
US (1) US5973006A (fr)
EP (1) EP0862551B1 (fr)
JP (1) JPH11513694A (fr)
AT (1) ATE193522T1 (fr)
AU (1) AU7285296A (fr)
CA (1) CA2233075A1 (fr)
DE (1) DE69608699T2 (fr)
DK (1) DK0862551T3 (fr)
ES (1) ES2148800T3 (fr)
GB (1) GB9521486D0 (fr)
GR (1) GR3034253T3 (fr)
PT (1) PT862551E (fr)
WO (1) WO1997015550A1 (fr)
ZA (1) ZA968795B (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998009938A1 (fr) * 1996-09-03 1998-03-12 Pharmacia & Upjohn S.P.A. Derives d'acide n-substitue-2-amino-4-phenyl-4-oxo-butanoique possedant une activite inhibitrice de kynurenine-3-hydroxylase
WO1999006375A1 (fr) * 1997-07-30 1999-02-11 Pharmacia & Upjohn S.P.A. Composes heterocycliques fondus et utilisation de ces composes comme inhibiteurs de la kynurenine-3-hydroxylase
US6858602B2 (en) * 2001-06-12 2005-02-22 Wellstat Therapeutics Corporation Compounds for the treatment of metabolic disorders
WO2016027757A1 (fr) * 2014-08-18 2016-02-25 国立大学法人大阪大学 Nouveau dérivé de 2-aminobenzoyle

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009065906A2 (fr) * 2007-11-20 2009-05-28 Cognis Oleochemicals Gmbh Procédé de fabrication d'une composition organique contenant un n-nonyléther

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0501378A1 (fr) * 1991-02-28 1992-09-02 Merrell Dow Pharmaceuticals Inc. Antagonistes du NMDA
WO1995003271A1 (fr) * 1993-07-23 1995-02-02 Pharmacia S.P.A. Derives de l'acide 2-amino-4-phenyl-4-oxobutyrique, ayant une activite inhibitrice de la cynureninase et/ou de la cynurenine-3-hydroxylase
WO1995004714A1 (fr) * 1993-08-06 1995-02-16 University Of Maryland At Baltimore Kynurenines substituees, procedes de preparation associe et d'utilisation comme medicaments

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0501378A1 (fr) * 1991-02-28 1992-09-02 Merrell Dow Pharmaceuticals Inc. Antagonistes du NMDA
WO1995003271A1 (fr) * 1993-07-23 1995-02-02 Pharmacia S.P.A. Derives de l'acide 2-amino-4-phenyl-4-oxobutyrique, ayant une activite inhibitrice de la cynureninase et/ou de la cynurenine-3-hydroxylase
WO1995004714A1 (fr) * 1993-08-06 1995-02-16 University Of Maryland At Baltimore Kynurenines substituees, procedes de preparation associe et d'utilisation comme medicaments

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998009938A1 (fr) * 1996-09-03 1998-03-12 Pharmacia & Upjohn S.P.A. Derives d'acide n-substitue-2-amino-4-phenyl-4-oxo-butanoique possedant une activite inhibitrice de kynurenine-3-hydroxylase
WO1999006375A1 (fr) * 1997-07-30 1999-02-11 Pharmacia & Upjohn S.P.A. Composes heterocycliques fondus et utilisation de ces composes comme inhibiteurs de la kynurenine-3-hydroxylase
US6858602B2 (en) * 2001-06-12 2005-02-22 Wellstat Therapeutics Corporation Compounds for the treatment of metabolic disorders
WO2016027757A1 (fr) * 2014-08-18 2016-02-25 国立大学法人大阪大学 Nouveau dérivé de 2-aminobenzoyle

Also Published As

Publication number Publication date
EP0862551A1 (fr) 1998-09-09
JPH11513694A (ja) 1999-11-24
US5973006A (en) 1999-10-26
ATE193522T1 (de) 2000-06-15
GR3034253T3 (en) 2000-12-29
DE69608699D1 (de) 2000-07-06
ZA968795B (en) 1997-05-20
EP0862551B1 (fr) 2000-05-31
GB9521486D0 (en) 1995-12-20
CA2233075A1 (fr) 1997-05-01
ES2148800T3 (es) 2000-10-16
PT862551E (pt) 2000-11-30
DE69608699T2 (de) 2000-11-23
AU7285296A (en) 1997-05-15
DK0862551T3 (da) 2000-10-02

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